NF-κB (nuclear factor KB) is a protein complex which serves as a transcription factor, and known to activate transcription of a variety of genes which control inflammation, immune reaction, cell proliferation, apoptosis and the like and HIV-1 (human immunodeficiency virus type 1), which is a causative virus of AIDS (acquired immunodeficiency syndrome). In addition, NF-κB is known to be constantly activated in inflammatory diseases such as Crohn's disease, bronchial asthma, inflammatory bowel disease, arthritis and sepsis and many malignant tumors. Therefore, it is thought that an inhibitor against NF-κB is effective in a treatment for these diseases.
NF-κB is usually associated with IκB (Inhibitor κB), a protein (inhibitor) which suppresses NF-κB activation, in the cytoplasm. It is known that: when a cell is stimulated by an inflammatory cytokine such as TNF-α (tumor necrosis factor-α) or IL-1 (interleukin-1), an IKK (IκB kinase) complex is activated by a kinase such as MEKK 1, 3 (mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1, 3) and NIK (NF-κB inducing kinase); the activated IKK complex phosphorylates two specific serine residues in IκB, and the phosphorylated IκB is polyubiquitinated and degraded by 26S proteasome; a nuclear localization signal (NLS) in NF-κB is then exposed; and NF-κB from which IκB is dissociated translocates into the nucleus and activates transcription of target genes.
In recent years, studies and development which position an NF-κB inhibitor as a candidate for a new antiinflammatory agent, antineoplastic drug and the like are vigorously carried out, and some NF-κB inhibitors consisting of a low molecular weight compound have been reported; such low molecular weight compounds have a variety of mechanisms of action. For example, PS-341 (Bortezomib), which is in a clinical trial for a therapeutic agent for myeloma, is a 26S proteasome inhibitor, and has been reported to show an inhibitory effect on NF-κB by suppressing degradation of IκB. It has been reported that DHMEQ (Dehydroxymethyl epoxyquinomycin) suppresses transcription activation by NF-κB by inhibiting nuclear import of NF-κB and induces apoptosis of a variety of myeloma cells. In addition, among gold compounds which are antirheumatic drugs, AuTG (aurothioglucose), in particular, has been reported to inhibit DNA binding of NF-κB through redox control. In addition, it has been reported that vitamin K2 suppresses activation of NF-κB by increasing the expression of IκB mRNA in osteoblasts and osteoclast precursor cells (Non-patent Document 1). Furthermore, it has been reported that S1627 suppresses transcription activation by NF-κB by inhibiting DNA binding of NF-κB, to increase bone formation and also improve osteopenia (Non-patent Document 2).
Up to now, the present inventors have carried out a basic study related to prevention and repair of osteoporosis by food factors. In the course of the study, they have reported ahead of the nation and foreign countries that, among edible marine algae, marine algae Sargassum horneri extract has an effect of promoting bone formation (Patent Document 1, Non-patent Documents 3 to 10). However, it was not clear whether the marine algae Sargassum horneri extract has an NF-κB inhibitory effect.